Non-infectious allergens (mixt-allergens) household group in the form of dragees

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Non-infectious allergens (mixed allergens) household group in the form of tablets

Composition:

Active substances: household mixed allergens (mixtures of allergens taken in equal proportions) of the following composition:

1 tablet contains household mixed allergen No. 5 (from house dust enriched with Dermatophagoides pteronyssinus; house dust enriched with Dermatophagoides farinae; house dust enriched with Acarus siro; pillow feathers);

Excipients: white sugar, molasses (glucose syrup), sodium chloride, disodium phosphate dodecahydrate, potassium dihydrogen phosphate, phenol, purified water.

1 tablet contains: 0.2 PNU (container No. 1), or 2.0 PNU (container No. 2), or 20.0 PNU (container No. 3), or 200.0 PNU (container No. 4), or 1000.0 PNU (container No. 5).

The product does not contain impurities or dyes.

Note: (1 PNU (Protein Nitrogen Unit) – an international unit accepted for determining the concentration of protein nitrogen in allergens, equivalent to 0.00001 mg of protein nitrogen).

Pharmaceutical form. Tablets.

Main physicochemical properties: spherical particles ranging from white to various shades of grey.

Pharmacotherapeutic group. House dust allergens.

ATC code V01A A03.

Immunological and biological properties.

Household allergens possess specific activity. The active component of household allergens is a protein-polysaccharide complex, which allows not only diagnosing the presence of sensitization to this allergen in a patient but also enables its further use for specific immunotherapy. Administration of allergens to sensitized individuals in gradually increasing doses (specific immunotherapy) leads to the development of immunological tolerance, which clinically manifests as reduction or complete disappearance of the main symptoms of allergic disease (manifestations of allergic rhinitis, bronchial asthma).

Pharmacodynamics. Not studied.

Pharmacokinetics. Not studied.

The effect of the drug is due to the combined action of its protein components, making pharmacokinetic studies impossible, as all components cannot be tracked using markers or biological assays. For the same reasons, metabolites of the drug cannot be identified.

Clinical characteristics.

Indications.

Specific immunotherapy for hypersensitivity (allergy) to relevant household allergens.

Contraindications.

To identify contraindications, the physician must examine the patient on the day of initiation of AIT.

Absolute contraindications

Severe immunopathological conditions and immunodeficiencies; oncological diseases; severe psychiatric disorders; acute infections and chronic infections in the exacerbation phase; somatic diseases with impaired function of corresponding organs and systems; inability of the patient to adhere to the prescribed treatment regimen; uncontrolled bronchial asthma (FEV1 less than 70% despite adequate pharmacotherapy, including severe bronchial asthma); cardiovascular diseases in which complications may occur with the use of adrenaline (epinephrine); use of beta-adrenergic antagonists (beta-blockers), including topical agents, and angiotensin-converting enzyme (ACE) inhibitors (for treatment of hypertension or ischemic heart disease); severe cardiovascular diseases; history of anaphylaxis during previous AIT; children under 3 years of age; systemic diseases; diabetes mellitus; uncontrolled thyrotoxicosis; myocardial infarction within the past year; persistent damage to the oral mucosa: ulcers, erosions; persistent periodontal disease; open wound in the oral cavity; recent tooth extraction or other oral surgical procedures; gingivitis with bleeding gums; oral cavity diseases (stomatitis, glossitis); severe inflammatory diseases of the oral mucosa (erythematous lichen planus, mycoses); acute or chronic gastrointestinal tract diseases (esophagitis, gastritis, peptic ulcer, enteritis, colitis, hepatitis); hypersensitivity to excipients of the medicinal product.

Relative or temporary contraindications

Age over 55 years; skin diseases; chronic infectious diseases; weakly positive skin tests with allergens; inefficacy of previous AIT (if performed); pregnancy and breastfeeding (see section «Use in pregnancy or lactation»); exacerbation of the underlying allergic disease; exacerbation of any concomitant disease; any intercurrent illness in the exacerbation phase; use of MAO inhibitors in combination with sympathomimetics; vaccination (see section «Special precautions»).

Limitations for AIT use

Insufficient patient understanding of the necessity of AIT and poor compliance; long duration of allergic disease (10 years or more); delayed positive skin tests with allergens; presence of non-specific hyperreactivity symptoms; sensitization to food, drug, or chemical allergens; marked hypersensitivity to 5 or more allergens.

Interaction with other medicinal products and other types of interactions.

AIT should not be performed during treatment with antibiotics, cytostatics, or immunobiological agents. It may be combined with medicinal products used for the treatment of allergic diseases (non-sedating antihistamines, cromones, bronchodilators, topical glucocorticosteroids, anti-leukotriene agents).

Special precautions for use.

Special warnings and preventive measures for the use of allergen preparations in the form of tablets are not required.

AIT must be performed only after the physician has obtained written informed consent from the patient!

AIT using sublingual tablets must be prescribed exclusively by an allergist or pediatric allergist experienced in the treatment of allergic diseases and who has undergone specialized training, including emergency management procedures for patients with anaphylaxis.

AIT should be performed on an outpatient basis; therefore, potential serious allergic reactions and the possibility of delayed systemic reactions to therapy must be thoroughly discussed with patients, and an action plan in such cases must be established.

AIT with mixed household allergens in the form of tablets should be administered only to patients in whom sensitization to these allergens has been confirmed by skin testing, in the absence of contraindications, and after the physician has obtained written informed consent from the patient!

Monitoring of treatment is advisable, with periodic patient examinations (initially daily, then each time a new tablet dose is initiated). Based on evidence-based data from global medicine regarding the safety of oral AIT, compliant patients (or parents of pediatric patients) may be entrusted with self-administration of the tablets, with periodic reporting to the allergist via telephone or email regarding treatment progress, well-being, and drug tolerability. In case of any adverse symptoms possibly related to AIT (onset or worsening of allergic disease symptoms, nausea, vomiting, stomach pain, skin rash, or itching), the patient must immediately visit the allergist. The patient should also visit the allergist at least once a month even if AIT is progressing normally.

Vaccination and AIT

Do not perform vaccination during the first phase of dose escalation of AIT.

It is advisable to perform routine vaccination one month before starting AIT or, if possible, postpone vaccination until after completion of the primary AIT course. For long-term AIT (continuous administration for 3 or more years), vaccination may be performed during the second phase of maintenance therapy, provided the following conditions are met:

• AIT and prophylactic vaccination should not be performed on the same day;
  • vaccination should be performed no earlier than 2–3 weeks after allergen administration;
• AIT may be continued no earlier than:
• 2 weeks after administration of inactivated vaccines;
• 4 weeks after administration of live vaccines;
• 8–12 weeks after administration of BCG vaccine;
• 1 week after tuberculin skin testing.

AIT should be resumed at the same dose used prior to vaccination.

The medicinal product contains sucrose in the amount of 2.85–14.25 g/dose (depending on the number of tablets taken by the patient); therefore, this product should not be administered to patients with diabetes mellitus.

The product contains glucose; therefore, patients with known intolerance to certain sugars should consult their physician before taking this medicinal product.

The medicinal product contains potassium and sodium compounds; however, their content is less than 1 mmol (39 mg)/dose of potassium and 1 mmol (23 mg)/dose of sodium, which allows the product to be considered practically free of potassium and sodium.

Use during pregnancy or breastfeeding.

Pregnancy is a relative contraindication for AIT (see section "Contraindications") due to the potential risk of systemic allergic reactions, which may lead to uterine contractions, and the need for epinephrine (adrenaline) administration, which may cause constriction of the umbilical artery.

AIT should not be initiated during pregnancy. If pregnancy occurs during ongoing AIT, further administration of allergens should be determined jointly by the allergist and the obstetrician-gynecologist, taking into account the potential risks to both mother and fetus in the event of a systemic allergic reaction or anaphylactic shock. Discontinuation of AIT is recommended if pregnancy occurs during the dose escalation phase. AIT may be continued if pregnancy occurs during the maintenance phase.

AIT should not be initiated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

No information available.

Method of Administration and Dosage

Household allergen mix tablets are intended for oral/sublingual administration.

The tablet should be slowly dissolved in the mouth (do not chew or swallow whole), ideally placed under the tongue! Do not drink water after administration!

Administration of allergen tablets should be performed no earlier than 1–2 hours after eating or 1–2 hours before eating! If a large number of tablets is prescribed (4–5), they do not need to be taken all at once; the dose may be divided and administered several times throughout the day.

Regimen for Allergen-Specific Immunotherapy (ASIT)

1. Tablets from container No. 1 (allergen content by protein nitrogen: 0.2 PNU) should be administered as follows: Day 1 – 1 tablet, Day 2 – 2 tablets, Day 3 – 3 tablets, Day 4 – 4 tablets, Day 5 – 5 tablets.

Administration of tablets from container No. 2 should begin the day after the last dose from container No. 1.

2. Tablets from container No. 2 (allergen content by protein nitrogen: 2.0 PNU) should be administered as follows: Day 1 – 1 tablet, Day 3 – 2 tablets, Day 5 – 3 tablets, Day 7 – 4 tablets, Day 9 – 5 tablets.

Administration of tablets from container No. 3 should begin two days after the last dose from container No. 2.

3. Tablets from container No. 3 (allergen content by protein nitrogen: 20.0 PNU) should be administered as follows: Day 1 – 1 tablet, Day 3 – 2 tablets, Day 6 – 3 tablets, Day 9 – 4 tablets, Day 12 – 5 tablets.

Administration of tablets from container No. 4 should begin one week after the last dose from container No. 3.

4. Tablets from container No. 4 (allergen content by protein nitrogen: 200.0 PNU) should be administered as follows: Week 1 – 1 tablet, Week 2 – 2 tablets, Week 3 – 3 tablets, Week 4 – 4 tablets, Week 5 – 5 tablets. Administration should occur on Mondays each week.

Administration of tablets from container No. 5 should begin two weeks after the last dose from container No. 4.

5. Tablets from container No. 5 (allergen content by protein nitrogen: 1000.0 PNU) should be administered at a dose of 1 tablet every 2 weeks (on the Monday of the second week).

Subsequently, tablets from container No. 5 should be taken (unless otherwise advised by the physician) once a month—2 tablets on the second Monday of each month—for a duration of 3 years or longer.

The duration of ASIT is determined by the allergist. The maximum therapeutic effect of ASIT typically develops 1–2 years after initiation. The optimal duration of ASIT is 3–5 years. If no therapeutic effect is observed after one year, ASIT should be discontinued.

Children

Allergen-specific immunotherapy with household allergen mix tablets is contraindicated in children under 3 years of age.

The ASIT regimen for children corresponds to the regimen used in adults.

When performing allergen-specific immunotherapy in children, current orders of the Ministry of Health of Ukraine must be followed.

Overdose

Exceeding the prescribed allergen dose during allergen-specific immunotherapy may lead to the development of adverse reactions in the patient.

Side effects.

When administering allergen-specific immunotherapy (ASIT) with allergens in the form of tablets, adverse reactions may occur very rarely.

Potential adverse reactions may develop 10 minutes or more after allergen administration and may manifest as:

• Respiratory, thoracic and mediastinal disorders: cough, dyspnea, bronchospasm, sneezing, nasal congestion and itching, throat irritation;
• Skin and subcutaneous tissue disorders: rash, facial flushing, urticaria, swelling, itching;
• Gastrointestinal disorders: nausea, vomiting, stomach or abdominal pain, diarrhea, some of which are dose-dependent;
• Nervous system disorders: headache, drowsiness;
• Psychiatric disorders: excitement;
• Eye disorders: eye redness, lacrimation;
• Musculoskeletal and connective tissue disorders: arthralgia;
• Immune system disorders: anaphylactic reactions;
• General disorders and administration site reactions: general weakness, increased body temperature, sensation of warmth throughout the body, oral itching, swelling of the oral mucosa, tongue swelling.

In case of mild adverse reactions, dose adjustment is required. These adverse reactions usually resolve spontaneously and do not necessitate discontinuation of treatment.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance associated with the use of the medicinal product. Healthcare professionals are required to report any adverse reactions through the national reporting system.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

15 tablets in medicinal containers and pharmaceutical containers (5 containers containing allergens: 0.2 PNU (container No. 1), 2.0 PNU (container No. 2), 20.0 PNU (container No. 3), 200.0 PNU (container No. 4), 1000.0 PNU (container No. 5)).

Packed as a set containing 75 tablets (15 tablets in each of containers No. 1, No. 2, No. 3, No. 4, and No. 5), placed in a cardboard box. The set includes a package leaflet for medical use.

For maintenance allergen-specific immunotherapy, 15 tablets in container No. 5 containing 1000.0 PNU of allergens are supplied separately.

Prescription category.

Prescription only.

Manufacturer/Marketing Authorization Holder.

LLC "Immunolog", Ukraine.

Manufacturer's address and location of its operations / Marketing Authorization Holder's and/or its representative's address.

5, Dmytro Mayborody Street, Vinnytsia, Vinnytsia Oblast, 21036, Ukraine.